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International Immunology Advance Access originally published online on June 25, 2009
International Immunology 2009 21(8):935-945; doi:10.1093/intimm/dxp060
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© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Nucleotide-hydrolyzing antibodies from the sera of autoimmune-prone MRL-lpr/lpr mice

Alexandra A. Andryushkova1, Irina A. Kuznetsova1, Irina A. Orlovskaya2, Valentina N. Buneva1 and Georgy A. Nevinsky1

1 Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, pr. Yadrintsovskaya 14, Novosibirsk 630090, Russia
2 Institute of Clinical Immunology, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk 630099, Russia

Correspondence to: G. A. Nevinsky; E-mail: nevinsky{at}niboch.nsc.ru

Abzymes (Abzs) with different enzymic activities have been detected in the sera of patients with various autoimmune (AI) diseases and in AI mice. In this work, electrophoretically homogeneous IgGs were isolated from the sera of MRL-lpr/lpr mice spontaneously developing lupus-like AI pathology. It was shown for the first time that polyclonal IgGs (pIgGs) and their isolated heavy and light chains hydrolyze different nucleoside-5'-triphosphate (NTPs), nucleoside-5'-diphosphate (NDPs), adenosine monophosphate and deoxiadenosine-5'-monophosphate (dAMP), whereas antibodies from the sera of control healthy mice were catalytically inactive. Monoclonal mouse IgGs also effectively hydrolyze nucleotides. The data demonstrate that nucleotide-hydrolyzing activity is an intrinsic property of isolated mouse pIgG and monoclonal IgG. It was shown that various markers of AI pathologies (proteinuria and antibody titers to native and denatured DNA) demonstrating spontaneous development of AI reactions increased in animals with aging and correlated with an increase in Abz relative activity in hydrolysis of nucleotides. The highest increase in AI reaction markers and in Abz enzymic activity was found in mice immunized with a DNA–protein complex.

Keywords: abzymes, hydrolysis of nucleotides, MRL-lpr/lpr mice

Transmitting editor: F. Andras

Received 7 February 2009, accepted 27 May 2009.


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